DESCRIPTION (provided by candidate): The purpose of this project is to develop a new method of imaging apoptosis, or programmed cell death. Programmed cell death is a regulated process that occurs normally within the body during which cells die in response to certain triggers without affecting neighboring healthy cells. Necrosis, another form of cell death, occurs when cells have been suddenly injured, leading to inflammation and extensive damage to surrounding tissues as a result. In many diseases there is either an excess of cell death, such as in sepsis where normally protective immune cells die, leaving the patient without an effective defense system to fight off the existing infection, or there is inadequate cell death, such as in cancer in which growing cells do not respond to normal cell death triggers. Therefore, it would be helpful to develop new imaging techniques which detect apoptosis specifically to identify tissues that are undergoing this process and would likely respond to treatments targeting this particular cell death pathway. This project will focus on the evaluation of two new classes of compounds that bind specifically in cells undergoing apoptosis and that can be used for positron emission tomographic imaging of cell death. The development of this technique for imaging cell death will have multiple clinical uses in helping physicians diagnose and treat disease. For example, this imaging technique may allow physicians to see whether a tumor responded to chemotherapy or not earlier, allowing the physician to change the chemotherapy treatment after just one cycle if needed instead of having to wait until finishing the entire chemotherapy course. In critically ill patients with sepsis, identifying the presence of severe apoptosis early may allow physicians to identify patients that need more aggressive care before organs begin failing. In neurodegenerative diseases, seeing how many neurons are dying may also help identify people who need more aggressive treatment and may also help physicians determine whether a treatment is working or not, again before significant damage occurs.